Application Effect Of Tyrosine Kinase Inhibitors In The Treatment Of Chronic Myeloid Leukemia

Objective To investigate Imatinib, Dasatinib and Nilotinib treatment of chronic myeloid leukemia (CML) clinical efficacy and survival, compare the relevant factors affecting curative effect, provide clinical basis for drug treatment of chronic myelogenous leukemia.Methods l)We collect patients who diagnose as chronic phase CML and take imatinib, monitoring the treatment process complete hematologic remission (CHR), complete cytogenetic response (CCyR), major molecular response (MMR), complete molecular remission (CMR) and related adverse reactions; 2) We also collect imatinib treatment failure (resistant or intolerant) taking nilotinib or dasatinib patients, monitoring the two drugs for the treatment of different diseases phases get CHR, CCyR, major cytogenetic response (MCyR) and related adverse reactions.Results 1) The team collected 243 patients taking tyrosine kinase inhibitor (TKIS) patients, including 150 cases of imatinib, nilotinib in 43 cases,50 cases of dasatinib. 2) Taking imatinib 150 patients,6-month CCyR was 60%,12-month MMR was 35%; To the end of follow-up, imatinib group CHR, CCyR, CMR were 98%,80%, 41%; 5-year PFS, OS were 80%,89%. Sokal low-risk, medium-risk group, high-risk group of 5-year PFS were 96%,79%,69%,5-year OS were 100%,88%,71%.150 patients enrolled hematologic adverse reactions, mainly for grade3 neutropenia 10% (15/150), grade 4neutropenia 2%(3/150), grade 3 thrombocytopenia 7%(10/150), grade 4 thrombocytopenia was 1.3%(2/150), non-hematologic adverse reactions mainly manifested as orbital edema peripheral 54%(81/150), muscle pain 45% (68/150),diarrhea 40%(60/150), headache 34%(51/150), of which non-hematologic grade 3/4 adverse reactions were mainly observed in liver function abnormalities 4.7% (7/150).3) Taking nilotinib therapy group for imatinib failure of 43 patients,43 cases of patients, including 23 cases of chronic phase, imatinib-resistant for 14 people (65%,14/23), including M351I 2 patients(14%), G250E 2 patients (14%), M244V 2 patients (14%), H396R 2 patients (14%), F317L 1 patient (7%), E355G 1 patient(7%), E459K 1 patient (7%), Q252H 1 patient (7%), V299L 2 patients (14%); imatinib intolerance for 9 people(35%,9/23); accelerated phase,20 cases for imatinib-resistant and 15 (75%, 15/20), including M315I 3 patients (20%), G250E 2 patients (13%), M244V 2patients (13%), H396R 1 patient (6%), F317L 2 patients (13%), E355G 1 patient (6%), E459K 2 patients (13%), Q252H 1 patient(6%), E255K 1 patient (6%); for imatinib intolerant 5 people(25%,5/20).o the end of follow-up,24-month chronic phase of patients CHR, CCyR, MCyR, OS, PFS were 75%,43%,52%,83%,60%; Patients with accelerated period of 24 months CHR, CCyR, MCyR, OS, PFS were 30%,20%,30%,67%,40%. Disease treatment process, the most common grade 3-4 non-hematologic adverse events included elevated lipase 14%(6/43), total bilirubin 9%(4/43).3-4 pleural effusion, pericardial effusion. Grade 3-4 hematologic adverse reactions in patients with chronic phase mainly for 17%(4/23), neutropenia,30%(7/23) thrombocytopenia, mainly for acceleration of 35%(7/20) neutropenia,40%(8/20) thrombocytopenia.4) Taking dasatinib group and imatinib treatment failure in 50 patients, of which 21 were in chronic phase (42%,21/50), for the 14 imatinib-resistant (67%,14/21), Including H369R1 cases (7%), F359V3 cases (20%), G250E2 cases (14%), M224V 1 case (7%), M351T 2 cases (14%), Y253H2 cases (14%), E255K3 cases (20%); for imatinib intolerance 7 (33%,7/21); acceleration of 23 (46%,23/50) for imatinib-resistant 20 people (87%,20/23), including L248V 1 case (4%), F359V 2 cases (10%), M224V 2 cases (10%), E355G 1 case (4%), Y253H 2 cases (10%), G250E 3 cases (15%), Q252H 1 cases, H396R 2 cases (10%), M351T3 cases (13%), E255K3 cases (15%); for imatinib-intolerant 3 (13%,3/23), CML 6 cases (12%,6/50), including two cases of acute myeloid variations (one case of E255V),2 cases of acute univariate (one case of E255K and 1 case of Q252H),2 patients with acute lymphoid (1 case of G250E).To the end of follow-up,24-month patients with chronic phase CHR, CCyR, MCyR,OS,PFS were 86%,52%,62%,76%,90%;Patients with accelerated phase of 24months CHR, CCyR, MCyR,OS,PFS were 48%,34%,40%,47%,70%; 6 patients with basis crisis, At the end of the follow-up to only 2 cases of live still in the treatment.Disease course of treatment Grade 3-4 hematologic adverse reactions:patients with chronic phase mainly for 48%(10/21) neutropenia,57%(12/21) thrombocytopenia, mainly in patients with accelerated phase was 70%(16/23) neutropenia,78%(18/23) thrombocytopenia. Pleural effusion was seen in 3 patients (2%) taking dasatinib.Conclusions1) The good efficacy and safety of imtinib is suitable for most patients with chronic myeloid leukemia,which is a first-line treatment for chronic myeloid leukaemia;2) Nilotinib, dasatinib as second-line drugs,for imatinib treatment failure in patients with chronic phase were significantly better than that of the advanced,early replacement drugs may be more effective to improve the prognosis of patients.3) For patients with advanced, second-generation tyrosine kinase inhibitor easy to relapse after remission induction,and adverse reactions are more serious than the patients with chronic phase.4) In the course of treatment for cytogenetic remission and molecular remission monitoring, can help to assess the efficacy of early and long-term prognosis.